Figure 1

Estimating the optimal drug combination from the mechanism of drug effects on viral replication. A) Conceptual diagram showing the effects of two anti-HCV drug effects on HCV replication. Drug A inhibits virus release, and drug B inhibits the production of viral polymerase. To calculate the effect of co-administered A and B on HCV production, the dynamics of each viral component during the replication are expressed by differential equations[37–40]. The presence of both drugs decreases the parameters, a production rate of viral proteins and a releasing rate of virions. B) Estimation of the optimal dose point in a drug combination. Each point (corresponding to a specific dose) denotes the difference between the effects of the combined drugs obtained by modeling the viral dynamics and the additive effects calculated by Loewe additivity. A positive (red) difference indicates that the drug combination surpasses the expected additive effect. At such synergistic dose points, the antiviral effect can be achieved by administering the drug in combination at doses below the single drug dose (the synergistic point).